dbSNP rs2273797: LMO2:c.464+68G>A (chr11-33864534-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_005574.4(LMO2):c.464+68G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.188 in 1,329,298 control chromosomes in the GnomAD database, including 24,799 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.20 ( 3307 hom., cov: 32)

Exomes 𝑓: 0.19 ( 21492 hom. )

Consequence

LMO2
NM_005574.4 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.592

Publications

5 publications found

Variant links:

Genes affected

LMO2 (HGNC:6642): (LIM domain only 2) LMO2 encodes a cysteine-rich, two LIM-domain protein that is required for yolk sac erythropoiesis. The LMO2 protein has a central and crucial role in hematopoietic development and is highly conserved. The LMO2 transcription start site is located approximately 25 kb downstream from the 11p13 T-cell translocation cluster (11p13 ttc), where a number T-cell acute lymphoblastic leukemia-specific translocations occur. Alternative splicing results in multiple transcript variants encoding different isoforms.[provided by RefSeq, Nov 2008]

LMO2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.268 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
LMO2	NM_005574.4 link	c.464+68G>A		intron_variant	Intron 5 of 5	ENST00000257818.3	NP_005565.2	P25791-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
LMO2	ENST00000257818.3 link	c.464+68G>A		intron_variant	Intron 5 of 5	1	NM_005574.4	ENSP00000257818.2		P25791-3

Frequencies

GnomAD3 genomes

AF:

0.204

AC:

31049

AN:

151906

Hom.:

3300

Cov.:

show subpopulations

Gnomad AFR

AF:

0.244

Gnomad AMI

AF:

0.248

Gnomad AMR

AF:

0.169

Gnomad ASJ

AF:

0.219

Gnomad EAS

AF:

0.274

Gnomad SAS

AF:

0.281

Gnomad FIN

AF:

0.210

Gnomad MID

AF:

0.306

Gnomad NFE

AF:

0.175

Gnomad OTH

AF:

0.207

GnomAD4 exome

AF:

0.186

AC:

219215

AN:

1177274

Hom.:

21492

AF XY:

0.189

AC XY:

111228

AN XY:

587092

show subpopulations

African (AFR)

AF:

0.245

AC:

6923

AN:

28238

American (AMR)

AF:

0.126

AC:

4735

AN:

37630

Ashkenazi Jewish (ASJ)

AF:

0.218

AC:

4655

AN:

21388

East Asian (EAS)

AF:

0.273

AC:

9929

AN:

36432

South Asian (SAS)

AF:

0.268

AC:

19247

AN:

71810

European-Finnish (FIN)

AF:

0.205

AC:

8401

AN:

41042

Middle Eastern (MID)

AF:

0.281

AC:

999

AN:

3558

European-Non Finnish (NFE)

AF:

0.174

AC:

154541

AN:

886562

Other (OTH)

AF:

0.193

AC:

9785

AN:

50614

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

9129

18258

27386

36515

45644

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

5280

10560

15840

21120

26400

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.204

AC:

31079

AN:

152024

Hom.:

3307

Cov.:

AF XY:

0.209

AC XY:

15541

AN XY:

74314

show subpopulations

African (AFR)

AF:

0.244

AC:

10108

AN:

41448

American (AMR)

AF:

0.169

AC:

2587

AN:

15292

Ashkenazi Jewish (ASJ)

AF:

0.219

AC:

762

AN:

3472

East Asian (EAS)

AF:

0.274

AC:

1413

AN:

5148

South Asian (SAS)

AF:

0.281

AC:

1347

AN:

4802

European-Finnish (FIN)

AF:

0.210

AC:

2227

AN:

10588

Middle Eastern (MID)

AF:

0.308

AC:

AN:

292

European-Non Finnish (NFE)

AF:

0.175

AC:

11888

AN:

67960

Other (OTH)

AF:

0.204

AC:

432

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1249

2498

3746

4995

6244

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.186

Hom.:

4501

Bravo

AF:

0.203

Asia WGS

AF:

0.255

AC:

887

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

0.13

(source)

DANN

Benign

0.68

PhyloP100

-0.59

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over